Arrowhead data reveal important considerations for future hepatitis B treatment

September 27, 2017

PASADENA, Calif., Sept. 27, 2017 -- Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced results from studies of ARC-520, a prior-generation RNAi therapeutic candidate against chronic hepatitis B virus (HBV) infection, in a Phase 2 clinical study in HBV patients and a complementary study in chimpanzees chronically infected with HBV. These studies demonstrated that HBV DNA integrated into the host genome is an under-appreciated source of HBV surface antigen (HBsAg), a key protein implicated in maintaining chronic HBV infection.

In many patients, integrated HBV DNA appeared to be the dominant source of HBsAg production. The findings expand the understanding of HBV biology and host interactions, and could have important implications for future trial design and endpoint expectations for new therapies developed to cure chronic HBV. These data from study, "RNAi-based treatment of chronically infected patients and chimpanzees implicates integrated hepatitis B virus DNA as a source of HBsAg" were published in Science Translational Medicine.

Bruce D. Given, M.D., chief operating officer and head of R&D for Arrowhead Pharmaceuticals, said: "Our experience from Arrowhead's multiple clinical studies of our prior therapeutic candidates ARC-520 and ARC-521, and the extensive non-clinical research we completed, have provided us with invaluable insights that guide the development path of follow-on candidate ARO-HBV, a new therapy for patients with chronic HBV that utilizes the company's next generation Targeted RNAi Molecule (TRiMTM) platform. We think long-term immune control of HBV will require reduction of HBsAg from both integrated DNA and cccDNA, which ARO-HBV is designed to do. Importantly, the findings described in the Science Translational Medicine paper extend beyond HBsAg in showing reductions in other viral antigens and viral DNA. The ARC-520 and ARC-521 data suggest that an RNAi-based approach, like ARO-HBV, could serve as a cornerstone therapy for combinations intended to cure chronic HBV because it can act as a direct anti-viral against all HBV viral products and has the potential to synergize with other agents."

The paper entitled, "RNAi-based treatment of chronically infected patients and chimpanzees implicates integrated hepatitis B virus DNA as a source of HBsAg," by Christine I. Wooddell and Man-Fung Yuen et al, was made available online ahead of print in the journal Science Translational Medicine (27 September 2017).

In the publication, several independent lines of evidence demonstrate that HBsAg is expressed not only from the episomal covalently closed circular DNA (cccDNA) minichromosome, but also from transcripts arising from HBV DNA integrated into the host genome. The latter was a large source of HBsAg production in HBeAg negative chimpanzees and presumed, by extension, in HBeAg negative and NUC experienced patients.

"This is an important finding with wide reaching implications for the field because production of viral proteins was previously thought to depend only on transcription of viral cccDNA. We now understand that that integrated HBV DNA is a means of producing circulating HBsAg that is not dependent on viral replication, which may contribute to sustained suppression of the immune system and allow for continued virion production," commented Christine I. Wooddell, Ph.D., lead study author. "Just a few cccDNA-containing cells able to escape immune surveillance can maintain chronic infection. Therefore, only complete immune control of HBsAg can be expected to prevent reinfection off therapy and result in a functional cure."
About Arrowhead Pharmaceuticals

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead's RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit, or follow us on Twitter @ArrowheadPharma. To be added to the Company's email list and receive news directly, please visit

Safe Harbor Statement under the Private Securities Litigation Reform Act:

This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of various factors and uncertainties, including the safety and efficacy of our product candidates, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the future success of our scientific studies, our ability to successfully develop drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, and the enforcement of our intellectual property rights. Our most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q discuss some of the important risk factors that may affect our business, results of operations and financial condition. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances.


Arrowhead Pharmaceuticals, Inc.
Vince Anzalone, CFA

Investors and Media:

LifeSci Advisors, LLC
Brian Ritchie

Source: Arrowhead Pharmaceuticals, Inc.

LifeSci Public Relations

Related Infection Articles from Brightsurf:

Halving the risk of infection following surgery
New analysis by the University of Leeds and the University of Bern of more than 14,000 operations has found that using alcoholic chlorhexidine gluconate (CHG) halves the risk of infection in certain types of surgery when compared to the more commonly used povidone-iodine (PVI).

How plants shut the door on infection
A new study by an international team including University of Maryland scientists has discovered the key calcium channel responsible for closing plant pores as an immune response to pathogen exposure.

Sensing infection, suppressing regeneration
UIC researchers describe an enzyme that blocks the ability of blood vessel cells to self-heal.

Boost to lung immunity following infection
The strength of the immune system in response to respiratory infections is constantly changing, depending on the history of previous, unrelated infections, according to new research from the Crick.

Is infection after surgery associated with increased long-term risk of infection, death?
Whether experiencing an infection within the first 30 days after surgery is associated with an increased risk of another infection and death within one year was the focus of this observational study that included about 660,000 veterans who underwent major surgery.

Revealed: How E. coli knows how to cause the worst possible infection
The discovery could one day let doctors prevent the infection by allowing E. coli to pass harmlessly through the body.

UK study shows most patients with suspected urinary tract infection and treated with antibiotics actually lack evidence of this infection
New research presented at this week's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam, Netherlands (April 13-16, 2019) shows that only one third of patients that enter the emergency department with suspected urinary tract infection (UTI) actually have evidence of this infection, yet almost all are treated with antibiotics, unnecessarily driving the emergence of antimicrobial resistance.

Bacteria in urine doesn't always indicate infection
Doctors should think carefully before testing patients for a urinary tract infection (UTI) to avoid over-diagnosis and unnecessary antibiotic treatment, according to updated asymptomatic bacteriuria (ASB) guidelines released by the Infectious Diseases Society of America (IDSA) and published in Clinical Infectious Diseases.

Subsidies for infection control to healthcare institutions help reduce infection levels
Researchers compared three types of infection control subsidies and found that under a limited budget, a dollar-for-dollar matching subsidy, in which policymakers match hospital spending for infection control measures, was the most effective at reducing the number of hospital-acquired infections.

Dengue virus infection may cause severe outcomes following Zika virus infection during pregnancy
This study is the first to report a possible mechanism for the enhancement of Zika virus progression during pregnancy in an animal model.

Read More: Infection News and Infection Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to